Protein kinase C zeta type - Mus musculus (Mouse)

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Q02956 (KPCZ_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 125. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Protein kinase C zeta type
EC=2.7.11.13

Alternative name(s):
nPKC-zeta

Gene names

Name:	Prkcz
Synonyms:	Pkcz

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	592 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. Is necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells By similarity. In inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukines production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In NF-kappa-B-mediated inflammatory response, can relieve the SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Ref.5 Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator By similarity.
Subunit structure	Interacts directly with SQSTM1. Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5 By similarity. Interacts with PARD6A, PARD6B and PARD6G. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with ADAP1/CENTA1. Interacts (via the protein kinase domain) with WWC1. Forms a tripartite complex with WWC1 and DDR1, but predominantly in the absence of collagen. Interacts with PDK1 (via N-terminus region) By similarity. Ref.4
Subcellular location	Cytoplasm By similarity. Endosome By similarity. Cell junction By similarity. Note: In the retina, localizes in the terminals of the rod bipolar cells. Associated with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction By similarity.
Domain	The C1 domain does not bind the diacylglycerol (DAG). The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B By similarity.
Post-translational modification	CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDK1; phosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 OPR domain. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Inflammatory response
Cellular component	Cell junction Cytoplasm Endosome
Domain	Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular signal transduction Inferred from electronic annotation. Source: InterPro microtubule cytoskeleton organization Inferred from mutant phenotype. Source: MGI
Cellular component	apical cortex Inferred from direct assay. Source: MGI endosome Inferred from electronic annotation. Source: UniProtKB-SubCell myelin sheath abaxonal region Inferred from direct assay. Source: BHF-UCL nuclear envelope Inferred from direct assay. Source: MGI nuclear matrix Inferred from direct assay. Source: MGI protein complex Inferred from direct assay. Source: MGI soluble fraction Inferred from direct assay. Source: MGI tight junction Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.6. Source: UniProtKB protein kinase C activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 592

592

Protein kinase C zeta type

PRO_0000055702

Regions

Domain

15 – 98

OPR

Domain

252 – 518

267

Protein kinase

Domain

519 – 590

AGC-kinase C-terminal

Zinc finger

130 – 180

Phorbol-ester/DAG-type

Nucleotide binding

258 – 266

ATP By similarity

Region

79 – 145

Interaction with SQSTM1 By similarity

Sites

Active site

376

Proton acceptor By similarity

Binding site

281

ATP By similarity

Amino acid modifications

Modified residue

410

Phosphothreonine; by PDPK1 By similarity

Modified residue

560

Phosphothreonine By similarity

Experimental info

Sequence conflict

197

D → G in AAA39983. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

Q02956 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 690AD891C25BC311
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FASTA

592

67,682

        10         20         30         40         50         60 
MPSRTDPKMD RSGGRVRLKA HYGGDILITS VDAMTTFKDL CEEVRDMCGL HQQHPLTLKW 

        70         80         90        100        110        120 
VDSEGDPCTV SSQMELEEAF RLVCQGRDEV LIIHVFPSIP EQPGMPCPGE DKSIYRRGAR 

       130        140        150        160        170        180 
RWRKLYRANG HLFQAKRFNR GAYCGQCSER IWGLSRQGYR CINCKLLVHK RCHVLVPLTC 

       190        200        210        220        230        240 
RRHMDSVMPS QEPPVDDKND GVDLPSEETD GIAYISSSRK HDNIKDDSED LKPVIDGVDG 

       250        260        270        280        290        300 
IKISQGLGLQ DFDLIRVIGR GSYAKVLLVR LKKNDQIYAM KVVKKELVHD DEDIDWVQTE 

       310        320        330        340        350        360 
KHVFEQASSN PFLVGLHSCF QTTSRLFLVI EYVNGGDLMF HMQRQRKLPE EHARFYAAEI 

       370        380        390        400        410        420 
CIALNFLHER GIIYRDLKLD NVLLDADGHI KLTDYGMCKE GLGPGDTTST FCGTPNYIAP 

       430        440        450        460        470        480 
EILRGEEYGF SVDWWALGVL MFEMMAGRSP FDIITDNPDM NTEDYLFQVI LEKPIRIPRF 

       490        500        510        520        530        540 
LSVKASHVLK GFLNKDPKER LGCRPQTGFS DIKSHAFFRS IDWDLLEKKQ TLPPFQPQIT 

       550        560        570        580        590 
DDYGLDNFDT QFTSEPVQLT PDDEDVIKRI DQSEFEGFEY INPLLLSAEE SV

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The cDNA sequence, expression pattern and protein characteristics of mouse protein kinase C-zeta." Goodnight J., Kazanietz M.G., Blumberg P.M., Mushinski F.J., Mischak H. Gene 122:305-311(1992) [PubMed: 1487145] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42." Joberty G., Petersen C., Gao L., Macara I.G. Nat. Cell Biol. 2:531-539(2000) [PubMed: 10934474] [Abstract] Cited for: INTERACTION WITH PARD6B. Tissue: Embryo.
[5]	"Control of T helper 2 cell function and allergic airway inflammation by PKCzeta." Martin P., Villares R., Rodriguez-Mascarenhas S., Zaballos A., Leitges M., Kovac J., Sizing I., Rennert P., Marquez G., Martinez-A C., Diaz-Meco M.T., Moscat J. Proc. Natl. Acad. Sci. U.S.A. 102:9866-9871(2005) [PubMed: 15987782] [Abstract] Cited for: FUNCTION IN INFLAMMATORY RESPONSE.
[6]	"Lysine methylation of the NF-kappaB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-kappaB signaling." Levy D., Kuo A.J., Chang Y., Schaefer U., Kitson C., Cheung P., Espejo A., Zee B.M., Liu C.L., Tangsombatvisit S., Tennen R.I., Kuo A.Y., Tanjing S., Cheung R., Chua K.F., Utz P.J., Shi X., Prinjha R.K. Gozani O. Nat. Immunol. 12:29-36(2011) [PubMed: 21131967] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M94632 mRNA. Translation: AAA39983.1. AL670413, AL670227 Genomic DNA. Translation: CAM20048.1. AL670227, AL670413 Genomic DNA. Translation: CAM20648.1. CH466594 Genomic DNA. Translation: EDL15000.1.
IPI	IPI00133596.
PIR	JC1480.
RefSeq	NP_032886.2. NM_008860.2.
UniGene	Mm.28561.
3D structure databases
ProteinModelPortal	Q02956.
SMR	Q02956. Positions 12-98, 130-587.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q02956. 1 interaction.
MINT	MINT-98101.
STRING	Q02956.
PTM databases
PhosphoSite	Q02956.
Proteomic databases
PRIDE	Q02956.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000030922; ENSMUSP00000030922; ENSMUSG00000029053.
GeneID	18762.
KEGG	mmu:18762.
NMPDR	fig\|10090.3.peg.11029.
Organism-specific databases
CTD	5590.
MGI	MGI:97602. Prkcz.
Phylogenomic databases
HOGENOM	HBG755340.
HOVERGEN	HBG108317.
InParanoid	Q02956.
OrthoDB	EOG4T782V.
PhylomeDB	Q02956.
Enzyme and pathway databases
BRENDA	2.7.11.13. 3474.
Gene expression databases
ArrayExpress	Q02956.
Bgee	Q02956.
CleanEx	MM_PRKCZ.
Genevestigator	Q02956.
GermOnline	ENSMUSG00000029053. Mus musculus.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR020454. DAG/PE-bd. IPR011009. Kinase-like_dom. IPR000270. OPR_PB1. IPR012233. PKC_zeta. IPR017892. Pkinase_C. IPR002219. Prot_Kinase_C-like_PE/DAG-bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K06069.
Pfam	PF00130. C1_1. 1 hit. PF00564. PB1. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
PIRSF	PIRSF000554. PKC_zeta. 1 hit.
PRINTS	PR00008. DAGPEDOMAIN.
SMART	SM00109. C1. 1 hit. SM00666. PB1. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS00479. ZF_DAG_PE_1. 1 hit. PS50081. ZF_DAG_PE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	294953.
SOURCE	Search...

Entry information

Entry name

KPCZ_MOUSE

Accession

Primary (citable) accession number: Q02956
Secondary accession number(s): A2AD76

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 27, 2011
Last modified:	January 25, 2012
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents